It is estimated that one third of the world's population carries a latent form of Mycobacterium tuberculosis (M.tb) infection. This global reservoir can reactivate at any given time that immunity is compromised, leading to active TB disease. With the recognized changes in immunity that occur as we grow older, the elderly are a significant rick group for reactivation TB. With the global elderly population projected to triple to almost 2 billion by the year 2050 we can anticipate that the elderly will make up a significant portion of al reactivation TB cases in the future. Few studies have been performed in M.tb infected elderly patients and much of what we understand about immune function has been generated using the aged mouse model, which is more susceptible to infection with M.tb and is reported to have poor CD4 T cell function. With the advent of new diagnostic kits for M.tb exposure we can now directly test the capacity of circulating immune cells from elderly TB patients to respond to M.tb antigens. There is a move towards the use of interferon gamma release assays (IGRA) in TB diagnosis, yet the sensitivity and applicability of IGRA versus the current tuberculin skin test (TST) in elderly individuals has not been tested. Our proposal will fill this critical gap in knowledge. We predict that the IGRA will provide a more accurate diagnosis of M.tb exposure in elderly individuals and our findings are likely to have immediate impact on the way that TB testing is performed in elderly cohorts. By performing translational studies we will address a specific knowledge gap to investigate immune function in elderly patients with active TB and latent M.tb infection that will allow us to better diagnose TB in this expanding population. PUBLIC HEALTH RELEVANCE: The elderly are more susceptible to reactivation of an infection with M. tuberculosis yet diagnosis of this specific group is challenging due to the poor diagnostic value of the tuberculin skin test (TST) in old age. With the advent of new in vitro diagnostic kits to determine M.tb exposure, there is a need to compare the sensitivity and applicability of these new tests in an elderly cohort. Our studies will fill this specific knowledg gap and are likely to have an immediate clinical impact on the diagnosis of M.tb in elderly individuals.